1. Field of the Invention
The present invention relates to an improved medicament inhalator. More particularly, the present invention relates to an improved dry powder medicament container usable by asthmatics and the like to facilitate proper deposition of the medicament in the lungs. The dry powder medicament inhalator uses a novel piercing mechanism and flow configuration to access the medicament and improve supply of the medicament to the lungs of the user.
2. State of the Art
The widespread existence of asthma and other respiratory disorders has lead to the development of numerous medications which can be used to open restricted breathing passages or otherwise enable the user to breathe more easily. While some asthmatics suffer from only occasional or minor attacks, for many breathing is a constant struggle made possible only by frequent use of appropriate medication. These medications may be in either dry or liquid form, depending on the type of medication and the particular problems faced by the user.
There are essentially two types of inhalation devices currently available in the marketplace for the administration of a medicament to the lungs. The predominant inhalation device is a pressurized, metered dose inhaler (MDI) which contains medicament suspended in a pharmaceutically inert liquid propellant, e.g., chlorofluorocarbons (CFCs) or hydrofluorocarbons (HFCs). MDIs are well known in the art and are commonly used.
These propellant-based inhalation devices have the advantage of consistently delivering a predetermined dose of medication from the aerosol canister. However, the drug particles are typically propelled at high velocity from the inhalation device. A significant quantity of the medication impacts tissue in the mouth or throat of the patient, becoming unavailable for deposition in the lungs. Furthermore, growing concern over the link between depletion of atmospheric ozone and chlorofluorocarbon propellants has focused attention on the development of alternative means of delivering medication to the lungs, including the development of dry powder inhalation systems.
Dry powder inhalers represent the second major type of inhalation devices. Dry powder inhaler devices known to the applicants and existing in the marketplace utilize the patient's inhaled breath as a vehicle to transport the dry powder drug to the lungs. Because the medicament is carried into the lungs during inhalation, less medicament is lost to the lining of the mouth and throat. Additionally, using the patient's inhalation increases the amount of medicament which reaches deep within the lungs where medicament is often needed most.
Presently there are four principal methods in use to provide fine particulate powder to the lungs without the use of chlorofluorocarbons or other propellants. One common method relies on the use of a hard gelatin capsule which contains a pre-measured dose of therapeutically active material and an inhalator device for use with the capsule. The capsule is placed in the inhalator device which serves to open or perforate the capsule, exposing the dose of medicament. The medicament is removed from the capsule by the vacuum action created when the patient inhales through the mouthpiece of the device, and is entrained in the inspired air stream for transport to the patient's lungs. The empty capsule is removed from the inhalation device after each use.
Inhalators using this type of capsule technology are described in U.S. Pat. No. 3,807,400 (Cocozza); U.S. Pat. No. 3,906,950 (Cocozza); U.S. Pat. No. 3,991,761 (Cocozza) and U.S. Pat. No. 4,013,075 (Cocozza). The intent in each of these devices is to remove all of the powdered medicament from the interior of the capsule. However, it has been found that the air stream generated by the patient is typically insufficient to accomplish complete removal of medicament from the capsule. This can be especially true for a patient having reduced inhalation ability due to an asthma attack.
Additionally, gelatin capsules are affected by relative humidity during storage and may become hydrated in moist environments. Hydration results in poor opening of the capsule and agglomeration of the powder contents. In dry climates, the capsules can become dehydrated, resulting in brittle fracture of the capsule, potentially making fine gelatin fragments available for inhalation or compromising dosing due to electrostatic attraction of medicament to the capsule surfaces.
A second method for delivery of dry powder medicaments relies on providing a package containing multiple doses of medicament, each contained in a sealed blister. The package is used in conjunction with a specially designed inhalation device which provides a means of attachment for the package and perforation of an individual blister by the patient prior to the inhalation of its contents. Delivery systems of this type are described in EPO Patent Application Publication No. 0 211 595 A2 (Newell et al.); EPO Patent Application Publication No. 0 455 463 A1 (Velasquez et al.); and EPO Patent Application Publication No. 0 467 172 A1 (Cocozza et al.). As the patient inhales, a portion of the inhaled air stream flows continuously through the perforated blister entraining the medicament and providing for inclusion of the medicament in the inspired breath. Delivery of medicament to the patient's inspired air stream begins as sufficient flow develops through the blister for removal of the medicament. No means is provided by which the point or rate of delivery of medicament to the patient is controlled.
A third method for delivery of dry powder medicaments involves the use of a device equipped with a drug reservoir containing sufficient medicament for a much larger number of doses. The Draco TURBUHALER® is an example of this type of device and is described in detail in U.S. Pat. No. 4,688,218 (Virtanen); U.S. Pat. No. 4,667,668 (Wetterlin); and U.S. Pat. No. 4,805,811 (Wetterlin). The device provides a means for withdrawing a dose of medicament from the reservoir and presenting the withdrawn dose for inhalation by the patient. As the patient inhales through the mouthpiece of the device, the medicament contained in perforations in a dosing plate is entrained in the inspired air and flows through a conduit or conduits. The conduits serve as a vortex creating a means for breaking up powder agglomerates before the medicament becomes available to the patient. Moisture ingress in the reservoir results in agglomeration of the powder contents, compromising dosing due to retention of powder in the perforations in the dosing plate and potentially inadequate breakup of particulates in the inspired air stream.
A fourth method for delivery of dry powder medicaments involves the use of a piston to provide air for either entraining powdered medicament, lifting medicament from a carrier screen by passing air through the screen, or mixing air with powder medicament in a mixing chamber with subsequent introduction of the powder to the patient through the mouthpiece of the device. Devices of this general type are described in PCT WO 93/12831 (Zirerenberg et al.); German Patent No. DE 4133274 A1 (Kühnel et al.); German Patent No. DE 4020571 A1 (Hochrainer et al.); and U.S. Pat. No. 5,388,572 (Mulhauser et al.). The incorporation of a piston system, in each case, adds to the complexity of the inhalation device, both in terms of use by the patient and device manufacturability.
A recent improvement in dry powder inhalators is contained in U.S. Pat. No. 5,988,163 for a Dry Powder Medicament Inhalator Having an Inhalation-Activated Flow Diverting Means for Triggering Delivery of Medicament. The inhalator disclosed therein utilizes a configuration which increases deep lung penetration of the medicament and reduces agglomerations.
While considerable progress in dry power inhalators has been made over the last decade, there is still considerable room for improvement. For example, in many configurations which use a blister pack, the medicament is accessed by advancing a lancet through the blister pack so that airflow will enter the top of the blister pack and exit through the bottom with the medicament entrained therein. Such configurations, however, have several distinct disadvantages.
First, as the blister pack is pierced by the lancet, it is not uncommon for the foil to be pushed out of the lancet's way in such a manner that the foil encapsulates or partially encapsulates a portion of the medicament. The deformed portions of the blister pack often prevent a portion of the medicament from being entrained in the airflow and thus reduce the amount of medicament going to the patient.
Second, advancing the lancet through the blister pack leaves an opening through which the medicament may fall. Usually, this does not present a problem, as the medicament will fall into a portion of the inspiratory flow channel and will be delivered properly once the user inhales. If, however, the lancet is accidentally actuated or the user forgets that the lancet has already been actuated, the blister pack may be advanced to position the next blister below the lancet while medicament remains in the inspiratory flow channel. Once the lancet has been actuated again and the user inhales, the user receives a double dose of the medicament. (If a child were to play with the inhalator and repeatedly advance and lance the blister pack, it is conceivable that a very large dose could be left within the inhalation channel of the inhalator.) With some asthma medications, accidentally supplying a double dose is undesirable and potentially dangerous to the patient.
Thus, there is a need for an improved medicament container and for a method and mechanism for actuating the same, wherein the container and inhalator controls medicament flow to ensure that the medicament is properly deposited in the lungs. Such a device preferably should be configured to release medicament into the inspiratory air stream and avoid leaving a therapeutically significant amount of medicament in the blister pack. Such a configuration should also inhibit simultaneous double or multiple dosing. Such a configuration should also be relatively inexpensive and convenient to use.